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  2. Bactericidal effect of pyridine-2-thiol 1-oxide sodium salt and its complex with iron against resistant clinical isolates of Mycobacterium tuberculosis

Bactericidal effect of pyridine-2-thiol 1-oxide sodium salt and its complex with iron against resistant clinical isolates of Mycobacterium tuberculosis

  • J Antibiot (Tokyo). 2020 Feb;73(2):120-124. doi: 10.1038/s41429-019-0243-3.
Debora L Campos 1 Ignacio Machado 2 Camila M Ribeiro 1 Dinorah Gambino 3 Fernando R Pavan 4
Affiliations

Affiliations

  • 1 Department of Biological Sciences, Faculty of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil.
  • 2 Área Química Analítica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
  • 3 Área Química Inorgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay.
  • 4 Department of Biological Sciences, Faculty of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara, SP, Brazil. fernando.pavan@unesp.br.
Abstract

The objective of this study was to determine the activity of pyridine-2-thiol 1-oxide sodium salt (Na mpo) and its complex with iron [Fe(mpo)3] against Mycobacterium tuberculosis. The compounds were tested against a standard strain of M. tuberculosis H37Rv (ATCC 27294), with minimal inhibitory concentrations (MIC90) of 7.20 and 1.07 μM to Na mpo and [Fe(mpo)3], respectively, and against three clinical isolates with different genotypic profiles, with MIC values ranging from 0.74 to 6.52 and 0.30 to 2.25 μM to Na mpo and [Fe(mpo)3], respectively. [Fe(mpo)3] was more effective against susceptible strains but both compounds were effective in inhibiting MDR and XDR-TB clinical strains. The profile activity was determined through the methodology of a time-kill curve against standard and clinical strains of M. tuberculosis. Time-kill studies indicated that Na mpo had an early bactericidal activity against H37Rv and clinical isolates, with sterilizing effects observed in 5 and 7 days, respectively, at its MIC90. The anti MDR and XDR-M. tuberculosis activity and bactericidal effect of Na mpo and [Fe(mpo)3] demonstrate their potential as new compounds for the treatment of tuberculosis.

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